Background: Lesbian, gay, bisexual, and transgender (LGBT) individuals have been identified as being at risk for health disparities by the Institute of Medicine. Compared to their heterosexual and non-transgender counterparts, they are especially likely to have higher rates of depression, posttraumatic stress disorder (PTSD), suicide ideation and attempt, alcohol misuse, and smoking. LGBT people are also overrepresented in the Veteran population compared to the general population, especially among women and transgender individuals. Recognizing this vulnerable population as a unique and sizable minority, the VA has made significant efforts to improve care for LGBT Veterans through consultation and staff trainings. Although research on LGBT Veterans has also increased, it has lagged behind, with only a small number of studies on LGBT Veterans to date. The available data suggest that LGBT Veterans experience a high burden of mental health problems and health risk behaviors, though studies have most often failed to examine differences by gender (combining women and men) or sexual identity (combining gay/lesbian and bisexual), and data on some sub-populations (e.g., gay and bisexual men) are extremely limited. Furthermore, few studies have examined the risk and protective factors that may explain these disparities, or LGBT Veterans? experiences with and preferences for treatment. Objectives: The objectives of this study are to: 1) identify the extent of sexual orientation and gender identity disparities in mental health problems (depression, PTSD, anxiety, suicide ideation/attempt) and health risk behaviors (alcohol misuse, smoking) among Veterans over time and across geographic regions; 2) examine risk and protective factors associated with these outcomes guided by a conceptual model that is informed by minority stress theory and the self-medication hypothesis; and 3) assess LGBT Veterans? experiences with and preferences for treatment, including VA utilization, barriers to care, and preferences for tailored interventions. Methods: This is a prospective cohort study with 1,600 Veterans that will address the three study objectives with 200 individuals in each of the following groups: heterosexual women, lesbian women, bisexual women, heterosexual men, gay men, bisexual men, transgender women, and transgender men. All Veterans will be recruited through online social networking sites and advertisements to online groups. Targeted advertisements will be used to recruit Veterans from sexual orientation and gender identity subgroups. Study assessments will also be conducted online to increase study reach and retention, with measures collected every nine months for 27 months (four assessments). This study targets HSR&D Priorities of Equity and Health Disparities as well as Improving Mental and Behavioral Health Interventions. Findings should greatly improve our knowledge about the extent of existing health disparities, the risk and protective factors associated with them, and treatment preferences of LGBT Veterans. They will also provide critical information for future prevention and intervention efforts for this stigmatized and highly vulnerable group.